The objective of this project is to determine the relative contributions of levo, alpha-acetylmethadol (LAAM) and its active metabolites to the pharmacological actions of the drug as can be deduced from pharmacokinetic and pharmacodynamic data obtained in rat, mouse, pregnant ewe and man. In rats and mice pharmacokinetic studies will be carried out in conjunction with the measurement of "analgesia" (tail-flick response) and other pharmacological effects seen following acute and chronic dosing with LAAM and metabolites. The distribution and elimination of LAAM and metabolite between mother and fetus after a single dose and at steady state will be determined using the chronic pregnant ewe preparation. Clinical analgesic assays of parenteral and oral LAAM and of parenteral methadone will be carried out in conjunction with pharmacokinetic studies in cancer patients with pain. Pharmacokinetic parameters at steady state will be determined from studies in LAAM maintenance patients. The analytical methods used in these studies will include: high pressure liquid chromatography, radiotracer techniques, mass spectrometry, gas-liquid chromatography and radioimmunoassay. These methods, together with solvent extraction, thin-layer and column chromatography, will provide quantitative and qualitative information on the disposition of LAAM in these species.